Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches

TitleElicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches
Publication TypeJournal Article
Year of Publication2017
AuthorsPauthner, M, Havenar-Daughton, C, Sok, D, Nkolola, JP, Bastidas, R, Boopathy, AV, Carnathan, DG, Chandrashekar, A, Cirelli, KM, Cottrell, CA, Eroshkin, AM, Guenaga, J, Kaushik, K, Kulp, DW, Liu, J, McCoy, LE, Oom, AL, Ozorowski, G, Post, KW, Sharma, SK, Steichen, JM, de Taeye, SW, Tokatlian, T, de la Pena, ATorrents, Butera, ST, LaBranche, CC, Montefiori, DC, Silvestri, G, Wilson, IA, Irvine, DJ, Sanders, RW, Schief, WR, Ward, AB, Wyatt, RT, Barouch, DH, Crotty, S, Burton, DR
JournalImmunity
Volume46
Issue6
Pagination1073 - +
Date Published2017/06/20/
ISBN Number1074-7613
Keywordsenv trimers, escape, glycoprotein complex, immunodeficiency-virus type-1, standardized assessments, target, tfh cells, vaccine design
Abstract

The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer. We identified immunogens that minimized non-neutralizing V3 responses and demonstrated that continuous immunogen delivery could enhance nAb responses. nAb responses were strongly associated with germinal center reactions, as assessed by lymph node fine needle aspiration. This study provides a framework for preclinical and clinical vaccine studies targeting nAb elicitation.

Short TitleImmunity